Effexor

INDICATIONS

Effexor (venlafaxine hydrochloride) is indicated for the
treatment of major depressive disorder.

The efficacy of Effexor in the treatment of major depressive
disorder was established in 6-week controlled trials of adult outpatients whose
diagnoses corresponded most closely to the DSM­III or DSM-III-R category of
major depression and in a 4-week controlled trial of inpatients meeting
diagnostic criteria for major depression with melancholia (see Clinical
Trials).

A major depressive episode implies a prominent and
relatively persistent depressed or dysphoric mood that usually interferes with
daily functioning (nearly every day for at least 2 weeks); it should include at
least 4 of the following 8 symptoms: change in appetite, change in sleep,
psychomotor agitation or retardation, loss of interest in usual activities or
decrease in sexual drive, increased fatigue, feelings of guilt or
worthlessness, slowed thinking or impaired concentration, and a suicide attempt
or suicidal ideation.

The efficacy of Effexor XR in maintaining an antidepressant
response for up to 26 weeks following 8 weeks of acute treatment was
demonstrated in a placebo-controlled trial. The efficacy of Effexor in
maintaining an antidepressant response in patients with recurrent depression
who had responded and continued to be improved during an initial 26 weeks of
treatment and were then followed for a period of up to 52 weeks was
demonstrated in a second placebo-controlled trial (see Clinical Trials).
Nevertheless, the physician who elects to use Effexor/Effexor XR for extended
periods should periodically re-evaluate the long-term usefulness of the drug
for the individual patient.

DOSAGE AND ADMINISTRATION

Initial Treatment

The recommended starting dose for Effexor is 75 mg/day,
administered in two or three divided doses, taken with food. Depending on
tolerability and the need for further clinical effect, the dose may be
increased to 150 mg/day. If needed, the dose should be further increased up to
225 mg/day. When increasing the dose, increments of up to 75 mg/day should be
made at intervals of no less than 4 days. In outpatient settings there was no
evidence of usefulness of doses greater than 225 mg/day for moderately depressed
patients, but more severely depressed inpatients responded to a mean dose of
350 mg/day. Certain patients, including more severely depressed patients, may
therefore respond more to higher doses, up to a maximum of 375 mg/day,
generally in three divided doses (see PRECAUTIONS, General, Use
in Patients with Concomitant Illness).

Special Populations

Treatment of Pregnant Women During the Third Trimester

Neonates exposed to Effexor, other SNRIs, or SSRIs, late in
the third trimester have developed complications requiring prolonged
hospitalization, respiratory support, and tube feeding (see PRECAUTIONS).
When treating pregnant women with Effexor during the third trimester, the
physician should carefully consider the potential risks and benefits of treatment.
The physician may consider tapering Effexor in the third trimester.

Dosage for Patients with Hepatic Impairment

Given the decrease in clearance and increase in elimination
half-life for both venlafaxine and ODV that is observed in patients with hepatic
cirrhosis and mild and moderate hepatic impairment compared to normal subjects
(see CLINICAL PHARMACOLOGY), it is recommended that the total daily dose
be reduced by 50% in patients with mild to moderate hepatic impairment. Since
there was much individual variability in clearance between subjects with
cirrhosis, it may be necessary to reduce the dose even more than 50%, and
individualization of dosing may be desirable in some patients.

Dosage for Patients with Renal Impairment

Given the decrease in clearance for venlafaxine and the
increase in elimination half-life for both venlafaxine and ODV that is observed
in patients with renal impairment (GFR = 10 to 70 mL/min) compared to normals
(see CLINICAL PHARMACOLOGY), it is recommended that the total daily dose
be reduced by 25% in patients with mild to moderate renal impairment. It is
recommended that the total daily dose be reduced by 50% in patients undergoing
hemodialysis. Since there was much individual variability in clearance between
patients with renal impairment, individualization of dosing may be desirable in
some patients.

Dosage for Elderly Patients

No dose adjustment is recommended for elderly patients on
the basis of age. As with any antidepressant, however, caution should be
exercised in treating the elderly. When individualizing the dosage, extra care
should be taken when increasing the dose.

Maintenance Treatment

It is generally agreed that acute episodes of major
depressive disorder require several months or longer of sustained pharmacological
therapy beyond response to the acute episode. In one study, in which patients
responding during 8 weeks of acute treatment with Effexor XR were assigned
randomly to placebo or to the same dose of Effexor XR (75, 150, or 225 mg/day,
qAM) during 26 weeks of maintenance treatment as they had received during the
acute stabilization phase, longer-term efficacy was demonstrated. A second
longer-term study has demonstrated the efficacy of Effexor in maintaining an
antidepressant response in patients with recurrent depression who had responded
and continued to be improved during an initial 26 weeks of treatment and were
then randomly assigned to placebo or Effexor for periods of up to 52 weeks on
the same dose (100 to 200 mg/day, on a b.i.d. schedule) (see Clinical Trials).
Based on these limited data, it is not known whether or not the dose of
Effexor/Effexor XR needed for maintenance treatment is identical to the dose
needed to achieve an initial response. Patients should be periodically
reassessed to determine the need for maintenance treatment and the appropriate
dose for such treatment.

Discontinuing Effexor (venlafaxine hydrochloride)

Symptoms associated with discontinuation of Effexor, other
SNRIs, and SSRIs, have been reported (see PRECAUTIONS). Patients should
be monitored for these symptoms when discontinuing treatment. A gradual
reduction in the dose rather than abrupt cessation is recommended whenever
possible. If intolerable symptoms occur following a decrease in the dose or
upon discontinuation of treatment, then resuming the previously prescribed dose
may be considered. Subsequently, the physician may continue decreasing the dose
but at a more gradual rate.

Switching Patients To Or From A Monoamine Oxidase Inhibitor

At least 14 days should elapse between discontinuation of an
MAOI and initiation of therapy with Effexor. In addition, at least 7 days
should be allowed after stopping Effexor before starting an MAOI (see CONTRAINDICATIONS).

HOW SUPPLIED

Effexor® (venlafaxine hydrochloride) Tablets are
available as follows:

25 mg, peach, shield-shaped tablet with “25” and a “W” on
one side and “701” on scored reverse side.

NDC 0008-0701-08, bottle of 60 tablets in unit of use
package.

37.5 mg, peach, shield-shaped tablet with “37.5” and a “W”
on one side and “781” on scored reverse side.

NDC 0008-0781-08, bottle of 60 tablets in unit of use
package.

50 mg, peach, shield-shaped tablet with “50” and a “W” on
one side and “703” on scored reverse side.

NDC 0008-0703-07, bottle of 30 tablets in unit of use
package.

75 mg, peach, shield-shaped tablet with “75” and a “W” on
one side and “704” on scored reverse side.

NDC 0008-0704-07, bottle of 30 tablets in unit of use
package.

100 mg, peach, shield-shaped tablet with “100” and a “W” on
one side and “705” on scored reverse side.

NDC 0008-0705-07, bottle of 20 tablets in unit of use
package.

The appearance of these tablets is a trademark of Wyeth
Pharmaceuticals.

Store at controlled room temperature 20° to 25°C (68° to
77°F) in a dry place.